Evidence map›Paper›PMID 31278196›Full record

ArticleJournal of the American Society of Nephrology : JASN2019

A Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection.

Weijia Zhang, Zhengzi Yi, Karen L Keung, Huimin Shang, Chengguo Wei, Paolo Cravedi, Zeguo Sun, Caixia Xi, Christopher Woytovich, Samira Farouk and 18 more

2 registry-linked trialsOpen access · greenAbstract readMulticenter Study
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01331668 recruitingnot on this map

Biobank Renal Transplantation University Hospitals Leuven

TypeobservationalSponsorUniversitaire Ziekenhuizen KU LeuvenRan2004 to 2099Enrolled5,000ConditionsKidney Failure
NCT07231328 not yet recruitingnot on this mapstarted 2025, after this paper: background citation

Post-Transplant Application of TruGraf and TRAC Molecular Panel in Renal Transplant Recipients

TypeobservationalSponsorTransplant Genomics, Inc.Ran2025 to 2029Enrolled600ConditionsImmunosuppression Management, Biomarkers / Blood, Subclinical Rejection, BiopsyArmsThere is no required Intervention for this Protocol. Based on Results for TruGraf/TRAC/TRAC ID Investigators may use the results in managing subjects Immunosuppression or rule out rejection.
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.

  1. Pooled it
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  6. Article
  7. Noninvasive Diagnosis of Kidney Allograft Rejection.Journal of the American Society of Nephrology : JASN · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Biomarkers of Rejection in Kidney Transplantation.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 9 institutions in 3 countries.

Weijia ZhangDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Zhengzi YiDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Karen L KeungDepartment of Medicine, Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia.
Huimin ShangDepartment of Microbiology and Immunology, Cornell Medical Center, New York, New York.
Chengguo WeiDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Paolo CravediDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Zeguo SunDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Caixia XiDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Christopher WoytovichDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Samira FaroukDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Weiqing HuangDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Khadija BanuDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Lorenzo GallonDepartment of Medicine-Nephrology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Ciara N MageeDepartment of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Nader NajafianDepartment of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Milagros SamaniegoDivision of Nephrology, Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
Arjang DjamaliDivision of Nephrology, Department of Medicine, University of Wisconsin, Madison, Wisconsin.ORCID 0000-0001-7675-6128
Stephen I AlexanderDepartment of Medicine, Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia.
Ivy A RosalesDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Rex Neal SmithDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Jenny XiangDepartment of Microbiology and Immunology, Cornell Medical Center, New York, New York.
Evelyne LerutDepartments of Pathology and.
Dirk KuypersDepartment of Microbiology and Immunology, Katholieke Universiteit Leuven, Leuven, Belgium.
Maarten NaesensDepartment of Microbiology and Immunology, Katholieke Universiteit Leuven, Leuven, Belgium.ORCID 0000-0002-5625-0792
Philip J O'ConnellDepartment of Medicine, Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia.
Robert ColvinDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Madhav C MenonDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Barbara MurphyDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; barbara.murphy@mssm.edu.
Icahn School of Medicine at Mount Sinai · USHarvard University · USThe University of Sydney · AUBrigham and Women's Hospital · USKU Leuven · BENewYork–Presbyterian Hospital · USHenry Ford Hospital · USNorthwestern University · USUniversity of Wisconsin–Madison · US

Funding

Genomics of Chronic Renal Allograft RejectionU01AI070107 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MURPHY, BARBARA T. · 2006 to 2012
$9.4M
NIAID NIH HHS U01 AI070107
6 · The paper itself

Abstract

backgroundIn kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies.

methodsWe examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant. We performed RNA sequencing on whole blood collected from 88 individuals at the time of 3-month surveillance biopsy to identify transcripts associated with ACR-3, developed a novel sequencing-based targeted expression assay, and validated this gene signature in an independent cohort.

resultsStudy participants with ACR-3 had significantly higher risk than those without ACR-3 of subsequent clinical acute rejection at 12 and 24 months, faster decline in graft function, and decreased graft survival in adjusted Cox analysis. We identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3, and validated it using microarray expression profiles of blood samples from 65 transplant recipients in the GoCAR cohort and three public microarray datasets. In an independent cohort of 110 transplant recipients, tests of the targeted expression assay on the basis of the 17-gene set showed that it identified individuals at higher risk of ongoing acute rejection and future graft loss.

conclusionsOur targeted expression assay enabled noninvasive diagnosis of subclinical acute rejection and inflammation in the graft and may represent a useful tool to risk-stratify kidney transplant recipients.

Indexed as

Gene Expression ProfilingAdultAgedBiomarkersBiopsyFemaleGenomicsGraft RejectionGraft SurvivalHumansImmunosuppressive AgentsInflammationKaplan-Meier EstimateKidney Failure, ChronicKidney TransplantationMaleBiomarkersImmunosuppressive Agentsacute rejectiongene expressionrenal transplantationwhole blood

Identifiers

PMID31278196
PMCPMC6683710
OpenAlexW2954143149

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.